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MEDICO-ECONOMIC EVALUATION OF SURGERY GUIDED BY FLUORESCENCE FOR THE OPTIMIZATION OF RESECTION OF GLIOBLASTOMAS (RESECT)

Primary Purpose

Glioblastoma

Status

Unknown status

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

5-aminolévulinique acid (5-ALA)

Placebo

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, 5ALA, fluorescence, resection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age greater than 18 years with no upper age limit
Competent adult patient.
Patient affiliated to the National Health Insurance.
Patient with an intra-cerebral supra-tentorial hemispheric, newly diagnosed and previously untreated, which MRI characteristics are suggestive of a glioblastoma.
Indication for surgical treatment by excision.
Brain tumor location distant from critical functional areas allowing a wide resection of contrast enhancement on imaging, the a priori character completely resectable has been validated by an evaluation committee composed of three surgeons
No-cons contain medical surgery, ASA score below 4.
Patient eligible for further treatment by radiotherapy and concurrent chemotherapy followed by adjuvant chemotherapy according to the so called Stupp scheme (standard protocol of adjuvant chemoradiotherapy)
Negative pregnancy test for women of childbearing age.

Exclusion Criteria:

Contraindications to performing an MRI (pacemaker).
- Glioblastoma known and previously treated with surgery, radiotherapy and / or chemotherapy.
- History of cancer.
- Anatomical Location of the tumor-cons indicating a wide excision, neurosurgeon at the discretion of medical officer participating center.
- Location tumor in the brain stem, the middle line, the basal ganglia and the posterior cranial fossa.
- Patient with cons-indication to the achievement of further treatment with radiotherapy and concurrent chemotherapy followed by adjuvant chemotherapy according to the scheme proposed by Stupp. (1)
- Patients with porphyria, renal insufficiency (creatinine> 177 μmolL), liver insufficency(gamma glutamyl transpeptidase> 100 U / L, prothrombin time <60%, bilirubin> 51μmol / L).
- Patient refused to sign an informed consent form.
- Ongoing participation of the patient to another clinical trial.

Sites / Locations

Guyotat

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

5-aminolévulinique acid (5-ALA)

Placebo

Arm Description

5-aminolévulinique acid :microsurgical resection guided by fluorescence (CGF) in addition to the usual techniques of neuronavigation, after oral administration of 20mg/kg of 5-ALA 3-5 hours prior to surgical incision

Laroscorbine :microsurgical excision guided solely by neuronavigation, after oral administration of a placebo 3 to 5 hours before the surgical incision

Outcomes

Primary Outcome Measures

Comparison of complete tumor resection between the 2 arms

Evidenced of complete resection (absence of residual tumor on early postoperative MRI (within 48 hours)) will be assessed by a central independent committee with qualitative analysis of contrast enhancement replay on a console for diagnostic use.

Secondary Outcome Measures

Comparison of complete tumor resection between the 2 arms

Evidenced of complete resection (absence of residual tumor on early postoperative MRI (within 48 hours)) will be assessed by the neurosurgeon who conducted the surgery and the neuro-radiologist who conducted the RMI with qualitative analysis of contrast enhancement replay during the initial clinical analysis

Full Information

NCT ID

NCT01811121

First Posted

February 21, 2013

Last Updated

October 4, 2016

Sponsor

Hospices Civils de Lyon

1. Study Identification

Unique Protocol Identification Number

NCT01811121

Brief Title

MEDICO-ECONOMIC EVALUATION OF SURGERY GUIDED BY FLUORESCENCE FOR THE OPTIMIZATION OF RESECTION OF GLIOBLASTOMAS

Acronym

RESECT

Official Title

Randomized, Prospective, Multicenter Blinding Singles With Arm A and Arm B Innovative Strategy Strategy Conventional

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Unknown status

Study Start Date

February 2013 (undefined)

Primary Completion Date

March 2013 (Actual)

Study Completion Date

August 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Glioblastoma is the most frequent primary malignant brain tumor in adults (3,000 new cases per year) and is characterized by a poor prognosis (median survival 12 months). Treatment is based mainly on surgical excision as complete as possible followed by an additional radiochemotherapy. The prognosis depends mainly on the quality of resection when it is macroscopically complete. Different techniques to support the surgical resection have been developed over the past 20 years. The reference technique is currently the intraoperative neuronavigation for guiding excision by matching the intraoperative tumor boundaries with those of the preoperative MRI. Its main drawback is the loss of precision during the resection related to changes in anatomical limits of the tumor. The per-operative fluorescence-guided surgery (FGS) is an innovative alternative technique to support the surgical resection. The 5-aminolevulinic acid (5-ALA), a molecule absorbed by the patient before surgery is captured specifically by the tumor cells and transformed into a fluorochrome revealed intraoperatively by a light source length adapted wave with a set of lenses included in the microscope. Resection is thus guided by this fluorescence whose disappearance translates complete tumor resection. Its interest is twofold: Increase the percentage of complete tumor resection. Improve disease-free survival and overall survival. The objective of the study is to compare the FGS to the intraoperative neuronavigation for the resection of glioblastoma, on a medical and economical level through a randomized, prospective, multicenter trial. The annual number of patients likely to benefit of this technique in France is estimated at 2200 new cases.

Detailed Description

Main Outcome Measure: Percentage of patients with surgical resection of the tumor is complete, objectified by the absence of residual tumor on MRI early postoperative (within 48 hours) by a central committee of independent reading with qualitative analysis taking a contrast replay console for diagnostic use

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

Keywords

Glioblastoma, 5ALA, fluorescence, resection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

170 (Actual)

8. Arms, Groups, and Interventions

Arm Title

5-aminolévulinique acid (5-ALA)

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Laroscorbine :microsurgical excision guided solely by neuronavigation, after oral administration of a placebo 3 to 5 hours before the surgical incision

Intervention Type

Drug

Intervention Name(s)

5-aminolévulinique acid (5-ALA)

Other Intervention Name(s)

Bras A

Intervention Description

oral administration of 20mg/kg of 5-ALA 3-5 hours before the surgical incision

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Bras B

Intervention Description

Oral administration of 1g of ascorbic acid LAROSCORBINE in 50ml of water 3 hours before surgery

Primary Outcome Measure Information:

Title

Comparison of complete tumor resection between the 2 arms

Description

Time Frame

48 hours

Secondary Outcome Measure Information:

Title

Comparison of complete tumor resection between the 2 arms

Description

Time Frame

less than 48 hours after surgery

Other Pre-specified Outcome Measures:

Title

Diagnostic value of the two intraoperative techniques

Description

Evaluate the sensitivity, specificity, positive predictive value and negative by correlating the results of pathological analysis of resection edge with intraoperative findings of the surgeon at the end of resection.

Time Frame

60 months

Title

Quantification of residual tumor (contrast enhancement) on MRI post-opératre early (before 48 hours)

Description

It will be performed by three study investigators (Dr. Pallud, Department of Neurosurgery, Centre Hospitalier Sainte-Anne, Paris; Dr. Guyotat, D department of Neurosurgery, Hospices Civils de Lyon, Lyon, Dr. Metellus, neurosurgery department, Assistance Publique - Hôpitaux de Marseille) and read separately. The volume analysis will be done by segmentation using the OsiriX software on postoperative MRI and MRI pre-operative

Time Frame

before 48 hours

Title

Progression Free survival rate at 6 months

Description

Progression is defined by the appearance of a new tumor lesion which minimum volume will be set to 0.175 cm3, by the increase of the residual tumor volume of 25% or more, or by the need to increase corticosteroid therapy. The period of progression free survival is defined as the time from the date of tumor resection and date of diagnosis of tumor progression or the date last news or date of endpoint. Progression Free survival rate at 6 months will be analyzed according to surgical approach used, according to the completeness or incompleteness of resection and by centers

Time Frame

6 months

Title

Overall survival at 24 months

Description

It will be estimated from the number of patients who died of whatever cause. The overall survival time is defined as the time between the date of tumor resection and date of death from any cause or date of last news or the date of endpoint. The overall survival at 24 months will be analyzed according to surgical approach used, according to the completeness or incompleteness of resection and by centers.

Time Frame

24 months

Title

Overall survival at 60 months

Description

It will be estimated from the number of patients who died of whatever cause. The overall survival time is defined as the time between the date of tumor resection and date of death from any cause or date of last news or the date of endpoint. The overall survival at 60 months will be analyzed according to surgical approach used, according to the completeness or incompleteness of resection and by centers.

Time Frame

60 months

Title

Quality of life

Description

Evaluation of quality of life every 3 months using the EORTC questionnaire QLQ-C30 with the specific brain tumors module BN20.

Time Frame

every 3 months

Title

Evaluation of early and late morbidity

Description

Evaluation of early morbidity in 8 days and late morbidity at 3 months (neurological deficit, surgical site infection, secondary epilepsy, Karnofsky score, performance status WHO).

Time Frame

in 8 days and late morbidity at 3 months

Title

Comparison of surgical procedure duration between the 2 arms

Time Frame

60 months

Title

Medico-economic evaluation of the 2 procedure

Description

Comparison of the differential cost effectiveness ratio between the 2 strategies

Time Frame

60 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age greater than 18 years with no upper age limit Competent adult patient. Patient affiliated to the National Health Insurance. Patient with an intra-cerebral supra-tentorial hemispheric, newly diagnosed and previously untreated, which MRI characteristics are suggestive of a glioblastoma. Indication for surgical treatment by excision. Brain tumor location distant from critical functional areas allowing a wide resection of contrast enhancement on imaging, the a priori character completely resectable has been validated by an evaluation committee composed of three surgeons No-cons contain medical surgery, ASA score below 4. Patient eligible for further treatment by radiotherapy and concurrent chemotherapy followed by adjuvant chemotherapy according to the so called Stupp scheme (standard protocol of adjuvant chemoradiotherapy) Negative pregnancy test for women of childbearing age. Exclusion Criteria: Contraindications to performing an MRI (pacemaker). Glioblastoma known and previously treated with surgery, radiotherapy and / or chemotherapy. History of cancer. Anatomical Location of the tumor-cons indicating a wide excision, neurosurgeon at the discretion of medical officer participating center. Location tumor in the brain stem, the middle line, the basal ganglia and the posterior cranial fossa. Patient with cons-indication to the achievement of further treatment with radiotherapy and concurrent chemotherapy followed by adjuvant chemotherapy according to the scheme proposed by Stupp. (1) Patients with porphyria, renal insufficiency (creatinine> 177 μmolL), liver insufficency(gamma glutamyl transpeptidase> 100 U / L, prothrombin time <60%, bilirubin> 51μmol / L). Patient refused to sign an informed consent form. Ongoing participation of the patient to another clinical trial.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jacques GUYOTAT, MD

Organizational Affiliation

Hospices Civils de Lyon

Official's Role

Study Director

Facility Information:

Facility Name

Guyotat

City

Lyon

Country

France

12. IPD Sharing Statement

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MEDICO-ECONOMIC EVALUATION OF SURGERY GUIDED BY FLUORESCENCE FOR THE OPTIMIZATION OF RESECTION OF GLIOBLASTOMAS

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